The primary objective is to estimate the size of the GR270773 treatment effect on 28-day all-cause mortality for two doses of GR270773 versus placebo in adult subjects with suspected or confirmed Gram-negative severe sepsis. GR270773 will be administered as a three-day continuous intravenous infusion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Enrollment
1,415
Percentage of Participants With 28-Day All Cause Mortality
Mortality was assessed by the number of participants who died between days 1 and 28. A summary of death details was given which included whether the participant died between days 1 and 28, whether the death was related sepsis, cause of death, the source of the information, and whether the cause of death was verified by a death record. Participants who had withdrawn from study and all study assessments and for whom survival at day 28 could not be confirmed was treated as deaths for the primary endpoint. The difference in all-cause 28-day mortality rates for each treatment group versus the placebo group in the ITT Population was calculated as placebo - treatment.
Time frame: Day 1 (post-infusion) up to Day 28 Follow-up
Number of Participants With New Onset Organ Failure, Regardless of Cause, Occurring During the 28 Days Post Enrollment in an Organ Not in Failure at Enrolment
The new onset organ failure was defined as first time each of the following criteria were met after start of study medication up to Day 28. Respiratory failure: defined by requiring mechanical ventilation not less than 24 hours due to surgery. Renal failure: defined by requiring the initiation of hemodialysis or hemofiltration. Coagulopathy: defined by disseminated intravascular coagulation (DIC) requiring transfusion with platelets or fresh frozen plasma or anticoagulant therapy. Cardiovascular failure: defined by sustained hypotension requiring vasopressor support of dopamine \>5 microgram per kilogram per minute (µg/kg/min), epinephrine, norepinephrine, phenylephrine or vasopressin at any dose if used to increase blood pressure for \>=6 continuous h. Analysis was done treating the death as a new onset organ failure (counted in both the numerator and denominator).
Time frame: Baseline (Day 1, pre-infusion) up to Day 28 Follow-up
Number of Participants With New Onset Organ Failure of Respiratory Failure, Cardiovascular Failure, Renal Failure and Coagulopathy, Regardless of Cause, Occurring During the 28 Days Post Enrollment in an Organ Not in Failure at Enrollment
Respiratory failure: defined by requiring mechanical ventilation not less than 24 hours due to surgery. Renal failure: defined by requiring the initiation of hemodialysis or hemofiltration. Coagulopathy: defined by disseminated intravascular coagulation (DIC) requiring transfusion with platelets or fresh frozen plasma or anticoagulant therapy. Cardiovascular failure: defined by sustained hypotension requiring vasopressor support of dopamine \>5 microgram per kilogram per minute (µg/kg/min), epinephrine, norepinephrine, phenylephrine or vasopressin at any dose if used to increase blood pressure for \>=6 continuous h. For each organ failure type and the number of new onset organ failures per participants for each organ failure type, the denominator only included participants who did not have that type of organ failure at Baseline. At Baseline a participant could enter the study with a type of organ failure, that type of failure was not reported as a new onset organ failure.
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GSK Investigational Site
Birmingham, Alabama, United States
GSK Investigational Site
Phoenix, Arizona, United States
GSK Investigational Site
Tucson, Arizona, United States
GSK Investigational Site
Tucson, Arizona, United States
GSK Investigational Site
Bentonville, Arkansas, United States
GSK Investigational Site
Little Rock, Arkansas, United States
GSK Investigational Site
Fresno, California, United States
GSK Investigational Site
Fullerton, California, United States
GSK Investigational Site
Loma Linda, California, United States
GSK Investigational Site
Los Angeles, California, United States
...and 380 more locations
Time frame: Baseline (Day 1, pre-infusion) up to Day 28 Follow up
Assessment of Safety/Tolerability by Determining the Number of Participants With Any Adverse Events (AE), Serious Adverse Events (SAE) and Fatal SAE
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition or common toxicity criteria (CTC) grade 4 laboratory abnormalities of national cancer institute not associated with the underlying sepsis unless more severe than expected for the participants condition.
Time frame: Day 1 (pre-infusion) up to Day 28 Follow-up